The long-term objective of this research is to determine how redundant genes in eukaryote genomes are regulated. The regulatory mechanisms responsible for structural maintenance of multiple copies and selected expression of the genes are of particular interest. The initial phases of this research are proposed here and focus on a combined genetic and molecular characterization of the histone genes in Drosophila melanogaster. Repeating units composed of one gene for each of the five major histone protein subtypes plus associated spacer sequences are clustered at polytene chromosome position 39 DE. The vast majority of the 110 such repeating units per haploid genome are 4.8 and 5.0 kb in size and are tandemly repeated, but other different and less abundant arrangements of histone sequences also exist. Strain specific polymorphism can exist in the histone locus in both the distribution of histone genes between the two major repeat sizes and in the complements of these less abundant arrangements. Recombinant DNA technology will be used to isolate less abundant arrangements of histone genes and they will be subsequently characterized to determine the molecular basis for this heterogeneity. Classical genetic and cytogenetic techniques will be used to accurately map the histone genes with respect to other markers on the second chromosome and to map the in situ location of variant sequences within the histone locus. Further experiments will measure variation in redundancy levels and will monitor changes in reiteration of histone genes in response to partial deficiencies and deletions at the histone locus. Polytenization of histone DNA sequences will also be studied for possible disproportionate replication. Additional experiments will study the homogeneity of histone repeating units within a species as well as the evolution of histone genes between different members of the genus Drosophila.